Rutacridone downregulates pi3k/akt signalling pathway and promotes mir-145 expression in cell cycle arrest and apoptosis of gastric cancer cells

SUMMARY. Ruta graveolens Linn. has been used traditionally as antiseptic, abortificient, anti-rheumatic, anti-inflammatory, anti-androgenic, and anti-hyperglycemic agent. The present study investigated the effect of rutacridone, a compound isolated from R. graveolens on gastric cancer cells and explored the un-derlying mechanism. The study demonstrated that treatment of AGS and NCI-N87 cancer cells with ru-tacridone significantly (p < 0.05) decreased cell viability but couldn’t affect normal, GES1 cell viability. Rutacridone treatment of AGS cells significantly (p < 0.05) increased apoptosis induction compared to the control cells. Moreover, treatment of AGS cells with rutacridone significantly (p < 0.05) increased percent-age of cells in the G1-phase of cell cycle. Additionally, treatment of AGS cells with 0.75 to 24 μM ru-tacridone caused a concentration-dependent decrease in invasion potential. It caused a marked increase in miR145 expression in AGS cells and reduced cMyc, PI3K, pAKT, MMP2 and MMP9 expression compared to the control cells. In summary, rutacridone inhibits gastric cancer cell viability in vitro by induction of cell apoptosis and arrest of cell cycle. Moreover, rutacridone promoted miR145 expression and down-regulation of PI3K/AKT signaling pathway in AGS cells. Therefore, rutacridone can be used as a potential therapeutic candidate for treatment of gastric cancer.